DESCRIPTION: The overall goal of this project is to exploit MR and CT volumetric imaging for evaluation and planning of pelvic brachytherapy treatments delivered as multiple insertions and/or in combination with external-beam therapy. Locally advanced carcinoma of the cervix is used as a clinical model to illustrate the challenging imaging science problems that must be solved to achieve this goal. To retain internal applicator shielding as a brachytherapy optimization strategy, high quality soft-tissue imaging in the presence of foreign metal objects is needed. A fundamental new approach to CT image reconstruction, constrained iterative deblurring (CID), is proposed as a solution to this problem. CID formulates the problem of image reconstruction as identifying that 3D image which minimized the penalized I-divergence between the measured and predicted spiral CT projections. CID reconstruction allows the known 3D geometry of intracavitary brachytherapy applicators and other metallic objects to be introduced as constraints on the iterative image reconstruction process in a fundamental and unified fashion. The ability to estimate total dose delivered to specific tissue voxels over a course of therapy is hindered by locally-variable displacement and deformation of anatomic structures due to tumor regression during therapy, insertion of vaginal and intrauterine applicators, filling and emptying of bladder and rectum, and edema following applicator or source insertion. We propose to solve this problem by applying the concept of individualized deformable neuroanatomies, used successfully to achieve image registration, image fusion and automatic image segmentation of soft tissue anatomy in the brain. For each pair of sequential imaging studies derived from a patient, the transformation that best matches the 3D volume or surface of each contoured organ in the two studies is found that is consistent with modeling each structure as a deformable elastic solid or fluid-filled volume. Finally, limited clinical studies are proposed to evaluate clinical and dosimetric significance of localized soft-tissue displacement and deformation from one imaging exam to another and to characterize the cumulative dose distributions within the target volume and critical structures typically achieved in definitive radiation therapy of locally-advanced cervix carcinoma.